Dehydroepiandrosterone induces growth arrest of hepatoma cells via alteration of mitochondrial gene expression and function.
DHEA is known to have anti-proliferative effect. The mechanism is not completely understood. We investigated the mechanism underlying DHEA-induced growth arrest of hepatoma cells. Growth inhibition was associated with increased G6PD activity, and insensitive to reversal by mevalonate. Thus, DHEA does not act via inhibition of G6PD and HMGR. Instead, growth stagnation was accompanied by reduced expression of nucleus-encoded mitochondrial genes; morphological and functional alterations of mitochondria; and depletion of intracellular ATP. Conversely, pyruvate supplementation alleviated DHEA-induced growth inhibition. It is likely that DHEA suppresses cell growth by altering mitochondrial gene expression, morphology and functions.
Ho
Hung-Yao
HY
Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC. hoh01@mail.cgu.edu.tw
Cheng
Mei-Ling
ML
Chiu
Hsin-Yu
HY
Weng
Shiue-Fen
SF
Chiu
Daniel Tsun-Yee
DT
D000255:Adenosine Triphosphate / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D004272:DNA, Mitochondrial / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D004734:Energy Metabolism; D015972:Gene Expression Regulation, Neoplastic; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008928:Mitochondria / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D013997:Time Factors
D004272:DNA, Mitochondrial; D003687:Dehydroepiandrosterone; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D006903:Hydroxymethylglutaryl CoA Reductases; D005954:Glucosephosphate Dehydrogenase